Lower risk of postinfarct rupture in mouse heart overexpressing β2-adrenergic receptors: Importance of collagen content

Xiao Ming Gao, Rodney J. Dilley, Chrishan S. Samuel, Elodie Percy, Meryl J. Fullerton, Anthony M. Dart, Xiao Jun Du

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22 Citations (Scopus)

Abstract

This paper addresses whether the enhanced left ventricular (LV) contractility and heart rate, seen in transgenic mice overexpressing β2-adrenergic receptor in the heart, might raise the incidence of LV rupture after myocardial infarct. Transgenic and wild-type mice underwent left coronary artery occlusion. Postinfarct deaths that occurred 1-7 days after surgery were analyzed. Hemodynamics, morphologic parameters, and collagen content in the LV were determined. A significantly lower incidence of LV rupture was observed in transgenic than in wild-type mice 3-5 days after myocardial infarct (2.5 versus 19.7%, p < 0.05), despite a similar infarct size between the two groups and better hemodynamic function in transgenic mouse hearts. Morphologic analysis showed a more severe infarct expansion in wild-type versus transgenic mice or in mice dying of rupture versus those that died of acute heart failure. Collagen content was higher in the LV of sham-operated transgenic than wild-type mice (p < 0.01) with both type I and type III collagen elevated. Such difference in collagen content between transgenic and wild-type mice was maintained in noninfarcted and infarcted LV. In conclusion, transgenic mice overexpressing β2-adrenergic receptor had a lower risk of cardiac rupture during the acute phase after infarction despite the markedly enhanced LV contractility and heart rate. As a hyperdynamic function due to β-adrenergic activation would likely increase the risk of cardiac rupture and infarct expansion, the lack of rupture in this transgenic mouse model suggests that the interstitial collagen level is a more important factor than functional status in the pathogenesis of rupture and infarct expansion.

Original languageEnglish
Pages (from-to)632-640
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume40
Issue number4
DOIs
Publication statusPublished - 1 Oct 2002
Externally publishedYes

Keywords

  • β-Adrenergic receptor
  • Cardiac rupture
  • Collagen content
  • Myocardial infarct
  • Transgenic mice

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